The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with pesticides and other agricultural exposures. The study is funded by the National Cancer Institute and the National Institute of Environmental Health Sciences, with collaboration from the US Environmental Protection Agency and the National Institute for Occupational Safety and Health. We are examining cancer incidence and other health endpoints in licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Between 1993 and 1997, we enrolled more than 57,000 licensed applicators, 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators completed a more detailed take-home questionnaire covering farming practices and health, and nearly 32,000 spouses of farmer applicators enrolled and provided data on reproductive health and children under age 21 at time of enrollment. After enrollment, study participants completed up to three follow-up surveys in 1999-2003, 2005-2010, and 2013-2015 respectively, updating data on farming exposures and lifestyle and the occurrence of cancer, non-cancer outcomes, and neurologic and respiratory symptoms. In addition to active follow-ups, the cohort is linked to cancer registries in IA and NC and vital statistics to identify cancer cases and deaths. We also collected buccal-cell samples for genetic research from about 40% of the study participants, as well as some specific cancers and other conditions, and we conducted a dietary survey as part of the 1999-2003 follow-up. Finally, we conducted in-depth pesticide exposure assessment for selected chemicals in targeted samples of the cohort. Results of these assessments have been used to validate study questionnaires and inform exposure classification. In addition to cancer, the AHS has been studying farming exposures in relation to neurological diseases and symptoms (Parkinson's disease, Alzheimer's disease, depression, neurobehavioral function, and suicide, amyotrophic lateral sclerosis), respiratory outcomes (e.g., chronic bronchitis), cardiovascular disease (heart attack, stroke), diabetes (gestational and adult onset), kidney and thyroid disease, autoimmune diseases (rheumatoid arthritis, lupus), age-related macular degeneration, fatal injury, and reproductive outcomes (infertility, fibroids and endometriosis) This work is led by NIEHS investigators. New research on neurologic outcomes includes ongoing analyses in the Farming and Movement Evaluation (FAME) study, and validation of new cases of Parkinson's disease has recently been completed (see report by F Kamel). Findings from an earlier report were supported by an updated analysis of medically confirmed macular degeneration in which we found that incident disease was associated with lifetime exposure to organochlorine insecticides and organophosphate insecticides and phenoxyacetate herbicides. In 2015, the AHS started a new sub-study on pesticides in relation to dementia and Alzheimer's disease. This collaboration is led by Dr. Plassman at Duke University and Drs. Kamel and Parks at NIEHS. We have screened the cognitive function of nearly 2500 elderly participants and identified about 16% with possible Alzheimers disease. Home visits, blood collection, and analyses are underway, and preliminary findings on pesticides associated with cognitive function were recently presented at a scientific meeting. NIEHS research on respiratory outcomes includes new published findings based on data from 2005-2010 on the relationship of pesticides with allergic and non-allergic wheeze, including 19 and 20 specific pesticide associations with allergic and non-allergic wheeze. Data analyses for an in-depth study of respiratory diseases involving a subcohort of applicators and spouses (The Lung Health Study) (see report by S London) are ongoing, while with new publications that show an inverse associations of perinatal and early childhood farm exposures with atopy (but not asthma), and an association of childhood raw milk consumption with higher lung function in adulthood. Related work showed increased residential endotoxin levels are associated with higher counts of peripheral white blood cells in the Lung Health Study as well as a general population sample. Following-up on prior research on pesticides and rheumatoid arthritis (RA) in female spouses, newly published findings on pesticides associated with incident RA risk in male applicators (Meyer et al, Environmental Health perspectives) show RA is associated with some specific pesticides, included a dose-response for lifetime days of atrazine use. Analyses of non-pesticide farming exposures (occupational factors and environmental dust) related to RA in famers are also ongoing, with results were presented at a meeting and a publication in preparation. We are also conducting a study of pesticides in relation to autoantibodies in a sample of 700 serum male farmers. Efforts are underway to confirm other autoimmune diseases, such as systemic lupus erythematosus, to support new analyses. In the Growth and Puberty Study, a pilot study to assess the feasibility of measuring early puberty markers (hormone levels in urine and saliva, height velocity, Tanner staging) in 60 children, hormone assays have been completed and their use in predicting puberty onset is being explored; preliminary findings were presented at a scientific meeting and a manuscript will be submitted shortly. A new analysis is exploring hormone levels in relation to children's potential pesticide exposure. Ongoing research has identified pesticide associations with incident hypothyroidism, confirming an earlier study of mostly prevalent cases. Initial findings, presented at a scientific meeting this past year, have been recently submitted for publication, including some consistent findings with newly published results on analyses of sub-clinical hypothyroidism in a subset of applicators. Collection of questionnaires and medical records for confirmation and validation of self-reported thyroid disease is nearly completed, which will facilitate interpretation of findings and future analyses. The AHS cohort continues to participate in large data pooling projects through the NCI-sponsored Cohort Consortium, and in the past year has contributed to a number of large scale pooling projects evaluating genetic and lifestyle/environmental risks for several cancers (e.g. breast, thyroid, ovarian cancers). The AHS is also one of the founding members of the Agricultural Cohort Consortium (AGRICOH) and we hope to use this collaboration to enhance our ability to assess rare exposures and outcomes. Half of the cohort is now over age 65, and so plans are underway to link AHS to administrative data on health outcomes in Medicare eligible AHS participants. This will enable studies of diseases that are difficult to study without validation and in participants lost to follow-up, reducing participant burden while facilitating research on aging-related diseases. Over the years, the Agricultural Health Study has contributed to our knowledge on potential health effects of exposures associated with pesticides use and other farming activities. This continuously serves our ultimate goal to improve the health of US farmers and their family members.